Making new cartilage from stem cells

Cartilage injuries have ended many athletes’ careers—including that of former two-sport star Bo Jackson—and the general wear-and-tear of the joint-cushioning tissue is something that almost everyone will endure as they age. Unfortunately, repairing cartilage remains difficult: Without blood flowing through it, cartilage has a hard time healing on its own and no chance of regenerating once it's gone.

Bioengineers are interested in finding innovative ways to grow new cartilage from a patient’s own stem cells. A new study from Jason Burdick, an associate professor in the Dept. of Bioengineering in the School of Engineering and Applied Science, and Robert Mauck, an associate professor of orthopedic surgery in the Perelman School of Medicine, brings such a treatment one step closer to reality.

At the core of their approach are mesenchymal stem cells, which are an adult stem cell found in bone marrow that can differentiate into bone, fat, or cartilage. Burdick and his colleagues are interested in the environmental cues that cause these stem cells to choose one of three different paths when the body is first developing. If the right cues could be simulated, a patient could have their own mesenchymal stem cells extracted and turned into chondrocytes, which can then grow into new cartilage.

The researchers simulate these environments by encapsulating mesenchymal stem cells in hydrogels, soft polymer networks that can mimic the physical and chemical environments in which cells naturally develop. Ideally, those hydrogels would then be implanted in the injured joint, allowing the growing cartilage to form within the damaged tissue. Unfortunately, hydrogels typically used in cartilage tissue engineering spread the cells apart, blocking signals they normally send to one another through direct contact.

“That’s when we started thinking about cadherins, which are molecules that these cells use to interact with each other, particularly at the point they first become chondrocytes,” Burdick says.

Using a peptide sequence that mimics these cadherin interactions, the researchers created a new kind of hydrogel that they hypothesized would ultimately encourage cartilage formation.

“What this gel does is trick the cell into thinking it’s got friends nearby,” Mauck says.

Compared to gels without the peptide, as well as ones that contained a scrambled, non-functional version, the researchers’ experimental gels performed better in genetic, chemical and physical tests of chondrocyte and cartilage formation.

Given the promising results, the next steps will involve testing these gels in load-bearing joints.